A novel technique for measuring human tissue pO2 at the cellular level

Some electron-affinic drugs, developed as hypoxic cell radiosensitizers, become selectively bound to the molecules of hypoxic cells by metabolism. This technique has been used to identify zones of chronically hypoxic cells in multicellular spheroids and animal tumours. Tritiated-misonidazole was administered to a patient with advanced melanoma 22 h prior to the surgical resection of a large metastatic s.c. lesion growing on the face. Autoradiographic analysis of histological sections revealed zones of intense labelling by the radioactive drug, indicative of tumour cells which were chronically hypoxic. This technique appears to provide an indirect measurement of tissue pO2 at the cellular level from which estimates of the tumour hypoxic fraction can be made. These data are encouraging as regards the development of 'sensitizer-adduct' procedures for the invasive and non-invasive measurement of hypoxia in both tumours and normal tissues.     

Covalent binding of a fluorinated 2-nitroimidazole to EMT-6 tumors in Balb/C mice: detection by F-19 nuclear magnetic resonance at 2.35 T

A hexafluorinated 2-nitroimidazole (CCI-103F) has been synthesized and its properties as a hypoxic cell binder investigated. The drug has a plasma half-life of 90 min in Balb/C mice and a tumor-to-plasma ratio of 0.8. Following sustained exposure to the drug and a washout period for the unbound drug, liver and tumor samples were excised. NMR investigation of the excised tissue in a 2.35 T animal sized NMR facility revealed the presence of 19F bound to both tissues. Further improvement in sensitivity is required to make 19F NMR detection of binding in situ feasible.     

Significant others benefit from preoperative information

Little attention has been given to the preparation of the patient's family prior to surgery, even though nurses' clinical experience suggests that family members are often more anxious than the patient. This study explored the knowledge and anxiety of spouses and significant others of patients preparing for cardiac surgery. The subjects were selected by convenience from a preoperative class offered at the hospital where surgery was to occur. Before and after the class, the subjects completed a cardiac-surgery knowledge test and an anxiety test. The significant others were significantly more anxious than the patients prior to the class. The anxiety level of significant others was significantly reduced after the class. There were no statistically significant differences between patients and significant others on the cardiac-surgery knowledge test. These results suggest that significant others may benefit from preoperative instruction.     

Cisapride or metoclopramide to accelerate small bowel transit during barium follow-through examination?

Background: Metoclopramide is commonly used to accelerate small bowel transit during barium follow-through (BaFT) examinations, but its action is unpredictable. Cisapride, commonly used to treat gastroesophageal reflux disease, also accelerates small bowel transit and may be a viable alternative. The two were compared in a prospective, randomized, blind study. Methods: Patients attending for BaFT were randomized to receive either 10 mg cisapride or 20 mg metoclopramide orally 1 h before the barium suspension. BaFT was performed by using a standard technique, and small bowel transit and study quality were compared. Patients also noted any side effects experienced. Results: Of 45 patients recruited, 27 received cisapride and 18 metoclopramide. Median transit time for the cisapride group was 30 min (range = 10–130 min) versus 67.5 min (range = 30–290 min) for the metoclopramide group (p= 0.019). Study quality was comparable. However, nine patients (33%) receiving cisapride experienced nausea versus only one subject (6%) receiving metoclopramide (p= 0.034). Conclusions: This study suggests that cisapride is a more effective prokinetic agent than metoclopramide, but this benefit is offset by a higher incidence of side effects. Received: 17 August 1999/Revision accepted: 3 November 1999     

Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial

BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES & MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.